Camptothecin (CPT) is an alkaloid which was extracted and isolated from camptotheca acuminate, a Chinese unique plant, by Wall, a US scientist, in 1966, and has remarkable activities against rat leukaemia L1210 system. Camptothecin is an alkaloid having a pyridone structure in its structure, and has a particular structure as follows,
In the structure, there is a pentacyclic structure, and Ring E is a 6-membered lactone ring containing an alpha-hydroxyl group in S-type absolute configuration. Camptothecin is of interesting due to its good activities against leukemia L1210, since it was extracted and isolated for the first time.
Thereafter, a series of camptothecin derivatives have gradually become new anticancer drugs that are already available in the market or in various development stages, for their unique bioactive mechanisms and good medicinal property, for example, 10-hydroxylcamptothecin (compound 2) widely applied in clinical therapy in China; 10-hydroxyl-9-dimethylaminomethylcamptothecin (compound 3, Topotecan) marked in 1996 and used as a second-line drug for treating ovarian cancer; compound 4 (SN-38) with excellent anti-tumor activity, and its water soluble prodrug, Irinotecan (compound 5) marked in 1994 and used for treating colorectal cancer; Belotecan (compound 6) approved for marketing in Korea in 2005 and used for treating prostatic cancer.

In addition, many other camptothecin derivatives are in various clinical trial stages. However, the current results indicate that these compounds have less curative effect than Topotecan or Irinotecan. Therefore, there is a need for camptothecin derivatives with better curative effect.
The existing camptothecin derivatives have drawbacks that lactone ring is unstable and may be opened to form an inactive structure under physiological conditions, which results in severe problems such as lowered curative effect and increased toxicity, as indicated as follows:

In order to solve this problem, homocamptothecin was suggested. The obtained compound 7 (Diflomotecan) has excellent anti-tumor activity and enter the phase III of clinical study. However, the clinical trial failed since the lactone ring thereof opened under physiological conditions could not be closed again under the same condition, as shown in the following reaction scheme:

Thus, it still needs novel camptothecin compounds with stable lactone ring.